Cortical Motor Regulation in Reeler Mutants

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K13053
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Rehabilitation science/Welfare engineering
• Research Institution: Osaka University
• Principal Investigator: Mariko Hiraga 大阪大学, 歯学研究科, 講師 (50638757)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 運動制御 / リーラーマウス

Outline of Final Research Achievements

To investigate the mechanism that underlies cortical reorganization in motor map of cerebral cortex, we tested the possibility that reelin signaling contributed to behavior-related cortical reorganization. Reelin, a lipoprotein released by Cajal Retzius cells, is required for the normal development of cerebral cortical layers. We first found that a higher current threshold to evoke a muscle movement was two-three times higher in the homozygous reeler mice than in the WT. The tendency in homozygous mutants that required a higher threshold in upper layers than in lower cortical layers was similar to that found in the WT, even though the neural-type distribution is reversed across the cortical layers in the homozygous. We also found the lack of reelin did not directly affect the innervation terminals to the skeletal muscles. We finally showed that a reduction in cortical reorganization and impairment in behavior-related cortical LTP in the heterozygous reeler mice.

Free Research Field

運動リハビリテーション

Academic Significance and Societal Importance of the Research Achievements

骨格筋－神経接合部位ではなく、大脳皮質や小脳でのリーリンの高次運動機能への関与が示された。ヒトの小脳萎縮では、骨格筋のatrophyが確認されていたが、reelinの発現低下から起こるのではなく、小脳萎縮に関連する運動機能障害による例えばdisuseから起こる2次的な結果だという事が明らかになった。リーリン発現の減少が起きる精神分裂症患者においても細かな高次運動機能の制限が認められているが、マウスモデルでは運動による運動野領域マップ再構築の低下及び、II/III層のLTP欠損を確認した。本成果はリーリンの高次機能可塑性への関与を示し、中枢神経運動機能疾患のさらなる原因解明が今後期待される。